Estradiol is a natural estrogen which has limited oral effectiveness because it is rapidly metabolized by the liver to estrone and its conjugates, giving rise to higher circulating levels of estrone than estradiol. In contrast, the skin metabolizes estradiol only to a small extent. Therefore, transdermal administration produces therapeutic serum levels of estradiol with lower circulating levels of estrone and estrone conjugates, and requires smaller total doses than does oral therapy. Since estradiol has a short half-life (about one hour), transdermal administration of estradiol allows a rapid decline in blood levels after a transdermal system is removed.
Estraderm.RTM. is an estradiol transdermal system available from CIBA Pharmaceutical Company. This system comprises four layers: a transparent polyester film; a drug reservoir of estradiol and alcohol gel with hydroxypropyl cellulose; an ethylene-vinylacetate copolymer membrane; and an adhesive formulation of light mineral oil and polyisobutylene for adhering the patch to skin.
Japanese Application 57075917 describes the manufacture of a tacky tape for use with a variety of sex hormones including valeric acid-estradiol. The tape is prepared by (1) copolymerizing (a) 60-98 parts by weight of dodecyl methacrylate, (b) 2-40 pts. wt. of a functional monomer and (c) 0-40 pts. wt. of at least one short chain unsaturated monomer selected from vinyl acetate, an alkyl acrylate, and an alkyl methacrylate; (2) combining the drug with the copolymer; and (3) spreading the resulting composition onto base material.
U.S. Pat. No. 3,598,123 describes a medical bandage for use with a variety of drugs including estradiol. The bandage comprises: a backing member and a layer of pressure-sensitive adhesive containing a plurality of discrete microcapsules containing the drug. Acrylic adhesives are specifically mentioned.
U.S. Patent No. 4,460,372 describes a transdermal device comprising a backing and an adhesive layer, the adhesive layer containing both estradiol and a microencapsulated percutaneous absorption enhancer such as ethanol.
GB Application 2158355 describes an estradiol containing transdermal dosage form comprising: a solid non-polymeric gel; a mixture of propylene glycol and glycerin; the therapeutic agent dispersed in the solvent mixture; and a thin, flexible, non-polymeric matrix in planar form. The mixture of propylene glycol and glycerine is described as enhancing the skin penetration of the therapeutic agent.
U.S. Pat. Nos. 3,598,122, 4,379,452, 4,573,996, 4,585,454, 4,624,665, and U.S. Pat. No. 4,460,372 (also mentioned above) all describe estradiol transdermal patches which include layers in addition to a backing and an adhesive layer. For example, many of these patents describe patches comprising a backing, a drug reservoir layer; a semipermeable membrane; and an adhesive layer coated on the exterior surface of the semipermeable membrane. Said U.S. Pat. No. 4,573,996 discloses a variety of penetration enhancers in Col. 11, lines 44-68
European Application 86.902978 5 describes a transdermal nitroglycerin delivery system comprising a flexible backing and a pressure-sensitive adhesive coating comprising an acrylic polymer and nitroglycerin. The adhesive coating may also comprise a skin penetration enhancing combination comprising a fatty acid ester of a fatty acid such as ethyl oleate and glyceryl monolaurate.
U.S. Pat. No. 4,722,941 discloses transdermal and oral formulations employing a fatty acid of medium chain length and optionally a monoglyceride of a saturated or unsaturated fatty acid of about 6 to 18 carbon atoms to enhance drug absorption. The formulations may include a steroid.
Glyceryl monolaurate, isopropyl myristate and ethyl oleate are known enhancers for transdermal administration of medicaments.